Sex and handedness differences in Big Five personality traits and depression: Investigating the role of cerebral lateralization

• Females scored significantly higher than males on neuroticism and agreeableness. • Right-handers scored higher in conscientiousness and extraversion, whereas left-handers scored higher in neuroticism. • No Big Five personality differences were found between consistent- and inconsistent-handers, and no sex interactions emerged.No Big Five personality differences were found between consistent- and inconsistent-handers, and no sex interactions emerged. • Females reported significantly higher depression scores compared to males, consistent with epidemiological patterns. • The combined effects of sex, handedness direction, and handedness consistency predicted depressive symptom levels. Brain lateralization, reflected in handedness, plays a role in cognitive and affective processing. While sex differences in personality and depression are well established, the combined effects of handedness and sex on these variables are not well understood. To address this gap, this study examined the associations of sex, handedness direction and consistency on personality and depressive symptoms in 198 European students (93 males, 105 females). Participants completed self-report inventories for personality (NEO-FFI), depression (BDI-II) and handedness (Edinburgh Handedness Inventory). MANOVA analyses revealed that females scored higher than males on neuroticism and agreeableness, consistent with previous research. Regarding handedness direction, right-handers showed higher conscientiousness and extraversion levels compared to left-handers, whereas left-handers scored higher in neuroticism. No main effects of handedness consistency on personality were observed. Females reported higher depression scores than males, consistent with epidemiological data. A significant interaction across sex, handedness direction and consistency indicated sex-specific vulnerability patterns. Specifically, consistent left-handed males and consistent right-handed females showed the highest depression scores, whereas inconsistent right-handed females and consistent right-handed males scored the lowest. These findings suggest that handedness and sex independently and interactively shape personality and depressive symptoms, emphasizing the role of lateralization and sex-specific neurobiological mechanisms in affective functioning.